Method of destroying microorganisms employing a phenylmercaptoalkyl isothiocyanate



United States Patent 3,085,045 METHOD 0F DESTROYHNG MHCROURGANISMSEMPLOYING A PHENYLMERCAPTOALKYL IS OTHIGCYANATE George E. Lukes,L'vington, N.Y., and Thomas C. Allen, In, Sunnyvale, Calif., assignorsto Staufier Chemical Company, New York, N .Y., a corporation of DelawareNo Drawing. Filed Sept. 27, 1961, Ser. No. 141,998

' 11 Claims. (Cl. 167-3t This invention relates to a method ofcontrolling the growth of microorganisms .such as fungi, bacteria andthe like by means of certain arylmercaptoalkyl isothiocyanates. Theinvention also'pertains to the formulation, use and application ofmicrobiocides, incorporating as the active principle thereof at leastone of the aforesaid arylmercaptoalkyl isothiocyanates.

It is known in the art to utilize organic isothiocyanates as a means ofinhibiting or otherwise controlling the growth of microorganisms such asthose of the type eX- emplified by fungi, bacteria and the like. Forinstance, methylisothiocyanate is a toxicant commonly used for thispurpose. More recently benzyl isot-hiocyanate has been proposed as afungicide and, in this connection, reference is made to British Patent825,693. Other organic isothiocyanates have been reported as exhibitingvarying degrees of biocidal activity.

With a view to improving the toxic properties of organicisothiocyanates, we have experimented with compounds which in additionto an isothiocyanate function, contain a substituted mercapto grouping,specifically a phenyl mercapto group. These dual function structureshave proved to be exceptionally potent in inhibiting the growth ofmicroorganisms and are thus valuable in formulating new and usefulpesticidal compositions.

It is therefore a primary object and aim of this inventionto providemicrobiocidal compositions, having as their active component at leastone of the aforedescribed dual function isothiocyanates. Anotherimportant object of the invention is to provide a method of preparing,using and applying such compositions. Other objects and purposes willbecome apparent as the description proceeds.

The compounds of this invention can be depicted formalistically by thegeneral formula as given below:

Ra Ra wherein at least one of R R and R represents hydrogen; loweralkyl; halogen e.g. bromine, chlorine etc.; a

.halomethyl group, e.g. fluoromethyl, dichloromethyl, trifiuoromethyletc; a lower alkoxy group e.g. methoxy,

ethoxy, n-propoxy, isopropoxy, sec-butoxy, n-butoxy etc.; and nitro.

As examples of structures falling within the ambit of the aforementionedformula, the following list is typical.

"ice

Compound 4: I

Br-OS-CH:NCS

Compound 5 I mQ-s-om-rros H300( -SCH2NCS Compound 9:

VINO: O-s-omums Compound 10:

'mo-Os om1sos Compound 11:

Compound 12:

Compound 13:

Compound 14:

mo-Q-s-om-uos Compound -15:

Compound '16:

Compound 17:

r-Qs-cm-rzos Compound 18:

Compound 20:

Compound 19:

The isothiocyanates of the type proposed herein are,

A foliage fungicide test is conducted in order to ascertain theprotectant action as well as eradicant and leaf systemic action of thetest compound-s. The particular type of action which is produced by thetest compound is determined by evaluation tests. Pinto bean plants aresprayed with various concentrations of the toxicant and, after drying,the plants are inoculated with bean rust or powdery mildew spores. Rustinfection requires an overnight treatment in a moisture ch-amberfollowing inoculation.

An agar plate fumigation test is carried out to determine whether thevapor of the compound is fungicidal. Approximately 0.1 gram of thetoxicant is placed in an 0.5 ml. micro beaker which is then located in aPetri dish of hardened potato dextrose agar. Aspergillus niger sporesare dusted over the agar surface and, after one week, the growth offungus is observed and recorded.

The results of carrying out the above described tests, using theisothiocyanate toxicants of this invention, are

in some cases, known chemical entities and their descrip- 20 reported inthe table below.

- Table [Approximate LD50 concentrations in p.p.rn.]

Fungi Bacteria Furnigant Compound Asper- Penicil- Rhiz- Rhiz0ct Fusa- E.Coli E. Amyl- S. Aspergillus lium opus v 01119. rium overa Aereus grllus(B) Botrytis.

phylium. .(X) Percent inhibition.

tion and preparation is detailed in the technical literature. Ingeneral, these compounds are formed by the chloromethylation of athiophenol, the reaction conditions being so adjusted thatchloromethylation occurs at the sulfur atom of the thiophenol. The.resulting S-chloromethylated product is next reacted with a metalthiocyanate such as an alkali metal thiocyanate whereby there isobtained an arylmercaptomethyl thiocyanate. The latter component is thenisomerized to the isothiocyanate structure by any number of well knownprocedures although heating is a method commonly employed to achievethis. Since arylthiophenols and numerous substituted derivatives thereofare well known chemical compounds and their chloromethylation can beeasily carried out, the arylsulfonylmethyl isothiocyanates of thisinvention are obtainable whenever the .aforesaid thiophenols can beprocured.

In using the isothiocyanate toxicants as contemplated herein, it ismerely necessary to contact them with the microorganism, the growth ofwhich it is desired to control. This can be accomplished by varioustechniques and procedures which are commonly employed in the pesticidalart. For instance, in vitro tests were conducted to measure thefungitoxicity of the herein contemplated toxicants when placed incontact with growing fungus or bacteria. In this procedure 1 oz. bottlesare partially filled with 10 ml. of malt or nutrient broth and cappedwith aluminum foil, sterilized and maintained for the test. A compoundis then injected by means of a syringe through the foil and into thebroth followed by inoculation with a water suspension of spores. Thebottles are then sealed and held for one week before the results areevaluated.

We claim: I

1. A method of inhibiting the growth of microorganisms which comprisesapplying thereto a small but effective amount of a phenylmercaptoalkylisothiocyanate of the type represented by the following general formula:

wherein R R and R are each selected from the class consisting ofhydrogen, lower alkyl, halogen, halomethyl, lower alkoxy and nitro.

2. A method of inhibiting the growth of microorganisms which comprisesapplying thereto a small but effective amount of a phenylmercaptoalkylisothiocyanate of the following formula:

Gs-curries 3. A method of inhibiting the growth of microorganisms whichcomprises applying thereto a small but effective amount of aphenylmercaptoalkyl isothiocyanate of the following formula:

4. A method of inhibiting the growth of microorganisms which comprisesapplying thereto a small but effective amount of a phenylmercaptoalkylisothiocyanate of the following formula:

5. A method of inhibiting the growth of microorganisms which comprisesapplying thereto a small but effective amount of a phenylmercaptoalkylisothiocyanate of the following formula:

6. A method of inhibiting the growth of microorganisms which comprisesapplying thereto a small but effective amount of a pheny-lmercaptoalkylisothiocyanate of the following formula:

H80 OOS-OH-NCS 7. A method of inhibiting the growth of microorganismswhich comprises applying thereto a small but effective amount of aphenylmercaptoalkyl isothiocyanate of the following formula:

moQ-s-om-rros 8. A method of inhibiting the growth of microorganismswhich comprises applying thereto a small but eifective amount of aphenylmercaptoalkyl isothiocyanate of the following formula:

QS-OHr-NGS 9. A method of inhibiting the growth of microorga- 6 nismswhich comprises applying thereto a small but effective amount of aphenylmercaptoalkyl isothiocyanate of the following formula:

Os-om-Nos 10. A method of inhibiting the growth of microorganisms whichcomprises applying thereto a small but effective amount of aphenylmer-captoalkyl isothiocyanate of the following formula:

11. A method of inhibiting the growth of microorganisms which comprisesapplying thereto a small but eifective amount of a phenylmercaptoalkylisothiocyanate of

1. A METHOD OF INHIBITING THE GROWTH OF MICROORGANISMS WHICH COMPRISES APPLYING THERETO A SMALL BUT EFFECTIVE AMOUNT OF A PHENYLMERCAPTOALKYL ISOTHIOCYANATE OF THE TYPE REPRESENTED BY THE FOLLOWING GENERAL FORMULA: 